We are investigating the mechanisms by which the mammalian egg processes sperm chromatin prior to the expression of the male genome in early embryo genesis. During spermatogenesis the somatic histones are replaced by cysteinerich protamines which form the nucleus into a morphologically dense structure. When isolated, these nuclei are extraordinarily resistant to chemical, physical and enzymatic attack. However, upon penetration into the egg's cytoplasm, the nuclei are rapidly processed in a series of reactions that include the reduction of disulfide bonds, the decondensation of the nuclei and the reconstitution of the DNA onto somatic histones. Using endonucleases as probes, we have demonstrated in vitro that after reduction and alkylation of purified sperm nuclei, we can mimic the decondensation and reconstitution steps with a polyacidic protein. We are now assaying the oocytes for the macromolecules that mediates these reactions in vivo.